Bone morphogenetic protein (BMP) signaling pathways play a role in the pathogenesis of rheumatoid arthritis (RA) and are downregulated although not completely inactivated by antirheumatic therapy, results show.
The finding is reported this month in the Annals of Rheumatic Diseases and is based on a study by Belgian researchers, who identified and characterized BMD target cells in the synovium of RA patients.
P Verschueren (Katholieke Universiteit Leuven) and team used needle arthroscopy to obtain synovial biopsies from 26 patients with early, active RA and three healthy controls. Protein extracts were then analyzed using antibodies against phosphorylated intracellular receptor-SMAD signaling molecules (P-SMAD1/5), which are induced by BMPs.
P-SMAD1/5 was detected in both RA and normal synovium, Verschueren et al report, with positive cells typically found in the perivascular and sublining cells.
Compared with normal tissue, however, synovium from RA patients had higher levels of P-SMAD1/5 expression. Diseased tissue also had different cell sub-populations, such as aSMA-positive perivascular cells located around von Willebrand factor-positive endothelial cells.
Finally, the authors showed that P-SMAD1/5 expression was reduced, although not completely eliminated, in patients receiving RA therapies.
“This study suggests that BMP biology may be relevant for fibroblast-like synoviocytes (FLS) and for angiogenesis in the synovium,” Verschueren and co-authors conclude.
“Our data may further support the concept that once RA has entered the chronic stage additional specific targeting of the FLS cell and more in particular the mesenchymal precursor cell population, for example via the BMP signaling pathway, may be an additional approach to restore full synovial homeostasis.”